Mos is normally expressed during oocyte meiotic maturation in vertebrates. However, apart from its cytostatic factor (CSF) activity, its precise role during mouse meiosis is still unknown. First, we analyzed its role as a MAP kinase kinase kinase. Mos is synthesized concomitantly with the activation of MAP kinase in mouse oocytes. Moreover, MAP kinase is not activated during meiosis in oocytes from mos -/- mice. This result implies that Mos is necessary for MAP kinase activation in mouse oocytes. Raf-1, another MAP kinase kinase kinase, is already present in immature oocytes, but does not seem to be active when MAP kinase is activated. Moreover, the absence of MAP kinase activation in mos -/- oocytes demonstrates that Raf-1 cannot compensate for the lack of Mos. These results suggest that Raf-1 is not involved in MAP kinase activation. Second, we analyzed the organization of the microtubules and chromosomes in oocytes from mos -/- mice. We observed that during the transition between two meiotic M-phases, the microtubules and chromosomes evolve towards an interphase-like state in mos -/- oocytes, while in the control mos +/- oocytes they remain in an M-phase configuration, as in the wild type. Moreover, after spontaneous activation, the majority of mos -/- oocytes are arrested for at least 10 hours in a third meiotic M-phase where they exhibit monopolar half-spindles. These observations present the first evidence, in intact oocytes, of a role for the Mos/.../MAP kinase cascade in the control of microtubule and chromatin organization during meiosis.